Exercise Muscle Biology Laboratory, Exercise Science Research Center, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR 72701 United States; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109 United States.
Department of Health and Exercise Science, Colorado State University, Fort Collins, CO 80523 United States.
Mech Ageing Dev. 2021 Mar;194:111404. doi: 10.1016/j.mad.2020.111404. Epub 2020 Nov 26.
The purpose of this study was to determine whether sarcopenic obesity accelerates impairments in muscle maintenance through the investigation of cell cycle progression and myogenic, inflammatory, catabolic and protein synthetic signaling in mouse gastrocnemius muscles. At 4 weeks old, 24 male C57BL/6 mice were fed either a high fat diet (HFD, 60 % fat) or normal chow (NC, 17 % fat) for either 8-12 weeks or 21-23 months. At 3-4 months or 22-24 months the gastrocnemius muscles were excised. In addition, plasma was taken for C2C12 differentiation experiments. Mean cross-sectional area (CSA) was reduced by 29 % in aged HFD fed mice compared to the aged NC mice. MyoD was roughly 50 % greater in the aged mice compared to young mice, whereas TNF-α and IGF-1 gene expression in aged HFD fed mice were reduced by 52 % and 65 % in comparison to aged NC fed mice, respectively. Myotubes pretreated with plasma from aged NC fed mice had 14 % smaller myotube diameter than their aged HFD counterparts. Aged obese mice had greater impairments to mediators of muscle maintenance as evident by reductions in muscle mass, CSA, along with alterations in cell cycle regulation and inflammatory and insulin signaling.
本研究旨在通过研究小鼠腓肠肌细胞周期进程和肌生成、炎症、分解代谢和蛋白质合成信号,确定肌少症性肥胖是否会加速肌肉维持的损伤。在 4 周龄时,24 只雄性 C57BL/6 小鼠分别用高脂肪饮食(HFD,60%脂肪)或正常饲料(NC,17%脂肪)喂养 8-12 周或 21-23 个月。在 3-4 个月或 22-24 个月时切除腓肠肌。此外,还采集了血浆用于 C2C12 分化实验。与老年 NC 喂养组相比,老年 HFD 喂养组小鼠的平均横截面积(CSA)减少了 29%。与年轻小鼠相比,老年小鼠的 MyoD 大约增加了 50%,而老年 HFD 喂养组的 TNF-α 和 IGF-1 基因表达分别比老年 NC 喂养组减少了 52%和 65%。用老年 NC 喂养组小鼠的血浆预处理的肌管,其肌管直径比老年 HFD 喂养组的肌管小 14%。肥胖老年小鼠的肌肉维持介质损伤更大,表现为肌肉质量和 CSA 减少,以及细胞周期调节、炎症和胰岛素信号改变。